This NIEHS training grant has been active for 36 years and has supported 112 pre-doctorates and 18 post-doctorates. It has significantly contributed to North Carolina State University's (NC State's) highly ranked training program in toxicology and continues to be the heart of NC State's Toxicology Program. NC State Toxicology Program doctoral graduates conduct basic and applied research, teach at universities and colleges, evaluate product safety and assist public agencies and private industries in resolving important public health and environmental problems. At each competitive renewal of this training grant, the investigators have strived to significantly revise, update, and improve their training program. In this competitive renewal of Molecular Pathways to Pathogenesis in Toxicology they have added eleven new training grant mentors who bring new skill sets involving epidemiology, quantitative biology, diverse model organisms, proteomics and epigenetics. While they plan to continue with the pathways to pathogenesis theme, the investigators have extended it to an overarching systems biology framework theme where their training program now aims to integrate all levels of biological organization: biomolecule, pathway, cell, tissue, organ, model organism, human, and human population to elucidate the fundamental mechanisms through which environmental stressors interface with pathways, the genome and epigenome to influence human health outcomes. The mission is to train the next generation of toxicologists/environmental health science scientists to be outstanding scientists capable of conducting high impact independent research as well as working as part of multidisciplinary teams aimed at understanding how human health, at the molecular, individual and population level, is impacted by environmental factors. There are twenty-three mentors from three colleges and four departments that are participating in this interdisciplinary training program. The revised academic curriculum trains students in fundamentals of toxicology, mechanistic molecular toxicology, environmental toxicology, molecular genetics, cell biology, and statistics and provides an introduction to exposure science and environmental epidemiology. Trainees receive training in ethics, grant writing and oral communication skills. Toxicology career workshops are planned to expose trainees to diverse career options. Trainees participate in a weekly seminar program both as members of the audience and as presenters. Each semester a former trainee is invited back to the department to present a seminar and to share their career experiences with current trainees. Trainees will conduct their research in many of the key strategic areas outlined in the NIEHS Strategic Plan 2012-2017 including but not limited to; fundamental mechanisms, GxE interactions, resistance and susceptibility to environmental stressors, effects of the environment on the genome and epigenome, individual and population susceptibility, critical windows of susceptibility, endocrine disrupting chemicals, integration of high-throughput screens, cell systems, and model organisms to identify fundamental mechanisms. The investigators are requesting support for six pre-doctoral trainees.